U.S. patent application number 11/897574 was filed with the patent office on 2008-03-06 for system and method for heightening an immune response.
This patent application is currently assigned to Searete LLC. Invention is credited to Muriel Y. Ishikawa, Edward K.Y. Jung, Nathan P. Myhrvold, Richa Wilson, Lowell L. JR. Wood.
Application Number | 20080059137 11/897574 |
Document ID | / |
Family ID | 35944463 |
Filed Date | 2008-03-06 |
United States Patent
Application |
20080059137 |
Kind Code |
A1 |
Ishikawa; Muriel Y. ; et
al. |
March 6, 2008 |
System and method for heightening an immune response
Abstract
The present application relates, in general, to a system and/or
method for detection and/or treatment.
Inventors: |
Ishikawa; Muriel Y.;
(Livermore, CA) ; Jung; Edward K.Y.; (Bellevue,
WA) ; Myhrvold; Nathan P.; (Medina, WA) ;
Wilson; Richa; (San Francisco, CA) ; Wood; Lowell L.
JR.; (Livermore, CA) |
Correspondence
Address: |
SEARETE LLC;CLARENCE T. TEGREENE
1756 - 114TH AVE., S.E.
SUITE 110
BELLEVUE
WA
98004
US
|
Assignee: |
Searete LLC
Bellevue
WA
|
Family ID: |
35944463 |
Appl. No.: |
11/897574 |
Filed: |
August 30, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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10926881 |
Aug 25, 2004 |
|
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11897574 |
Aug 30, 2007 |
|
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Current U.S.
Class: |
703/11 |
Current CPC
Class: |
G16B 30/00 20190201;
C07K 16/00 20130101; A61K 39/00 20130101; G16C 20/50 20190201 |
Class at
Publication: |
703/011 |
International
Class: |
G06G 7/60 20060101
G06G007/60 |
Claims
1. A method, comprising: providing one or more antigenic attributes
of one or more agents associated with at least a part of an immune
response in a host; and forming a set of the one or more antigenic
attributes operable for modulating the at least a part of the
immune response in the host.
2. The method of claim 1, wherein the forming a set of the one or
more antigenic attributes further comprises: forming a set
including the one or more antigenic attributes displayed by the one
or more agents.
3. The method of claim 1, wherein the forming a set of the one or
more antigenic attributes further comprises: forming a set
including the one or more antigenic attributes present in a copy
number of at least two and displayed by the one or more agents.
4. The method of claim 1, wherein the forming a set of the one or
more antigenic attributes further comprises: forming a set
including the one or more antigenic attributes present in at least
two of the one or more agents.
5. (canceled)
6. (canceled)
7. The method of claim 1, further comprising: displaying one or
more sequences corresponding to the one or more antigenic
attributes of the one or more agents.
8. The method of claim 1, further comprising: projecting one or
more alternate courses of the at least a part of the immune
response in the host associated with the one or more antigenic
attributes of the one or more agents.
9. The method of claim 1, wherein the providing one or more
antigenic attributes of one or more agents associated with at least
a part of an immune response in a host further comprises:
projecting at least one pattern of change in the one or more
antigenic attributes of the one or more agents associated with the
at least a part of the immune response in the host.
10. The method of claim 9, wherein the projecting at least one
pattern of change in the one or more antigenic attributes of the
one or more agents associated with the at least a part of the
immune response in the host further comprises: projecting at least
one pattern of change in the one or more antigenic attributes of
the one or more agents in response to a treatment.
11. The method of claim 1, wherein the forming a set of the one or
more antigenic attributes operable for modulating the at least a
part of the immune response in the host further comprising: forming
a set of the one or more antigenic attributes of the one or more
agents amenable to a treatment.
12. The method of claim 11, wherein the treatment includes: a
treatment of at least a part of at least one of an antibody, a
recombinant antibody, a genetically engineered antibody, a chimeric
antibody, a monospecific antibody, a bispecific antibody, a
multispecific antibody, a diabody, a human antibody, a
heteroantibody, a monoclonal antibody, a polyclonal antibody, or an
antibody fragment.
13. The method of claim 11, wherein the treatment includes: a
treatment of at least a part of at least one of a macrophage, a
lymphocyte, an immune response modulator, an antigen receptor, an
antigen presenting cell.
14. The method of claim 11, wherein the treatment includes: a
treatment of at least one modulator of at least a part of at least
one of an antibody, a recombinant antibody, a genetically
engineered antibody, a chimeric antibody, a monospecific antibody,
a bispecific antibody, a multispecific antibody, a diabody, a human
antibody, a heteroantibody, a monoclonal antibody, a polyclonal
antibody, or an antibody fragment.
15. The method of claim 11, wherein the treatment includes: a
treatment of at least one modulator of at least a part of at least
one of a macrophage, a lymphocyte, an immune response modulator, an
antigen receptor, or an antigen presenting cell.
16. (canceled)
17. (canceled)
18.-36. (canceled)
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application is related to, claims the earliest
available effective filing date(s) from (e.g., claims earliest
available priority dates for other than provisional patent
applications; claims benefits under 35 USC .sctn.119(e) for
provisional patent applications), and incorporates by reference in
its entirety all subject matter of the following listed
applications; the present application also claims the earliest
available effective filing date(s) from, and also incorporates by
reference in its entirety all subject matter of any and all parent,
grandparent, great-grandparent, etc. applications of the following
listed applications: [0002] 1. United States patent application
entitled A SYSTEM AND METHOD RELATED TO IMPROVING AN IMMUNE SYSTEM
naming Muriel Y. Ishikawa, Edward K. Y. Jung, Nathan P. Myhrvold,
Richa Wilson, and Lowell L. Wood, Jr. as inventors, filed 24 Aug.
2004. [0003] 2. United States patent application entitled A SYSTEM
AND METHOD RELATED TO ENHANCING AN IMMUNE SYSTEM naming Muriel Y.
Ishikawa, Edward K. Y. Jung, Nathan P. Myhrvold, Richa Wilson, and
Lowell L. Wood, Jr. as inventors, filed 24 Aug. 2004. [0004] 3.
United States patent application entitled A SYSTEM AND METHOD
RELATED TO AUGMENTING AN IMMUNE SYSTEM naming Muriel Y. Ishikawa,
Edward K. Y. Jung, Nathan P. Myhrvold, Richa Wilson, and Lowell L.
Wood, Jr. as inventors, filed 24 Aug. 2004. [0005] 4. United States
patent application entitled A SYSTEM AND METHOD FOR MAGNIFYING AN
IMMUNE RESPONSE naming Muriel Y. Ishikawa, Edward K. Y. Jung,
Nathan P. Myhrvold, Richa Wilson, and Lowell L. Wood, Jr. as
inventors, filed contemporaneously herewith.
TECHNICAL FIELD
[0006] The present application relates, in general, to detection
and/or treatment.
SUMMARY
[0007] In one aspect, a method includes but is not limited to:
providing one or more antigenic attributes of one or more agents
associated with at least a part of an immune response in a host;
and forming a set of the one or more antigenic attributes operable
for modulating the at least a part of the immune response in the
host. In addition to the foregoing, other method aspects are
described in the claims, drawings, and text forming a part of the
present application.
[0008] In one or more various aspects, related systems include but
are not limited to circuitry and/or programming for effecting the
herein-referenced method aspects; the circuitry and/or programming
can be virtually any combination of hardware, software, and/or
firmware configured to effect the herein-referenced method aspects
depending upon the design choices of the system designer.
[0009] In addition to the foregoing, various other method and or
system aspects are set forth and described in the text (e.g.,
claims and/or detailed description) and/or drawings of the present
application.
[0010] The foregoing is a summary and thus contains, by necessity;
simplifications, generalizations and omissions of detail;
consequently, those skilled in the art will appreciate that the
summary is illustrative only and is NOT intended to be in any way
limiting. Other aspects, inventive features, and advantages of the
devices and/or processes described herein, as defined solely by the
claims, will become apparent in the non-limiting detailed
description set forth herein.
BRIEF DESCRIPTION OF THE FIGURES
[0011] FIG. 1 is a diagrammatic view of one aspect of an exemplary
interaction of an immune response component, for example, an
antibody interacting with an epitope displayed by an agent.
[0012] FIG. 2 is a diagrammatic view of one aspect of a method of
enhancing an immune system.
[0013] FIG. 3 depicts one aspect of an antigen antibody interaction
showing the occurrence of mutational changes in a selected epitope
and corresponding changes in a complementary antibody.
[0014] FIG. 4 is an illustration of one aspect of mutational
changes in an epitope displayed by an agent and the corresponding
changes in an immune response component, for example, an
antibody.
[0015] FIG. 5 depicts a high-level logic flow chart of a
process.
[0016] FIG. 6 depicts a high-level logic flowchart depicting
alternate implementations of the high-level logic flowchart of FIG.
5.
[0017] FIG. 7 depicts a high-level logic flowchart depicting
alternate implementations of the high-level logic flowchart of FIG.
5.
[0018] FIG. 8 depicts a high-level logic flowchart depicting
alternate implementations of the high-level logic flowchart of FIG.
5.
[0019] FIG. 9 depicts a high-level logic flowchart depicting
alternate implementations of the high-level logic flowchart of FIG.
5.
[0020] FIG. 10 depicts a high-level logic flowchart depicting
alternate implementations of the high-level logic flowchart of FIG.
5.
[0021] FIG. 11 depicts a high-level logic flowchart depicting
alternate implementations of the high-level logic flowchart of FIG.
5.
[0022] FIG. 12 depicts a high-level logic flowchart depicting
alternate implementations of the high-level logic flowchart of FIG.
5.
[0023] FIG. 13 depicts a high-level logic flowchart depicting
alternate implementations of the high-level logic flowchart of FIG.
5.
[0024] FIG. 14 depicts a partial view of a system that may serve as
an illustrative environment of and/or for subject matter
technologies.
[0025] FIG. 15 depicts a partial view of a system that may serve as
an illustrative environment of and/or for subject matter
technologies.
[0026] The use of the same symbols in different drawings typically
indicates similar or identical items.
DETAILED DESCRIPTION
[0027] The present application uses formal outline headings for
clarity of presentation. However, it is to be understood that the
outline headings are for presentation purposes, and that different
types of subject matter may be discussed throughout the application
(e.g., device(s)/structure(s) may be described under the
process(es)/operations heading(s) and/or process(es)/operations may
be discussed under structure(s)/process(es) headings). Hence, the
use of the formal outline headings is not intended to be in any way
limiting.
[0028] With reference now to FIG. 1, depicted is a diagrammatic
view of one aspect of an exemplary interaction of an immune
response component, for example, an antibody interacting with an
epitope displayed by an agent. Accordingly, the present application
first describes certain specific exemplary methods of FIG. 1;
thereafter, the present application illustrates certain specific
exemplary structures. Those having skill in the art will appreciate
that the specific structures and processes described herein are
intended as merely illustrative of their more general counterparts.
It will also be appreciated by those of skill in the art that an
antigen-antibody interaction is an exemplary interaction of the
interaction of an immune response component with an antigen.
Therefore, although, the exact nature of the interaction may vary
the overall picture as described herein and in other related
applications relates to the interaction of an immune response
component interacting with the antigen.
[0029] A. Structure(s) and or System(s)
[0030] With reference to the figures, and with reference now to
FIG. 1, depicted is a diagrammatic view of one aspect of an
exemplary interaction of an immune response component, for example,
an antibody 104 interacting with an epitope 102 displayed by an
agent 100.
[0031] The term "agent" 100 may include, for example, but is not
limited to, an organism, a virus, a bacterium, a yeast, a mold, a
fungus, a mycoplasma, an ureaplasma, a Chlamydia, a rickettsia, a
nanobacterium, a prion, an agent responsible for a transmissible
spongiform encephalopathy (TSE), a multicellular parasite, a
protein, an infectious protein, a nucleic acid, a metabolic by
product, a cellular by product, and/or a toxin. The term "agent"
100 may include, but is not limited to, a putative causative agent
of a disease or disorder, a cell that is deemed, for example, a
target for therapy, a target for neutralization, and/or or a cell
whose removal may prove beneficial to the host. The term "agent"
100 may also include, but is not limited to, a byproduct of a cell
that may be neutralized and/or whose removal may prove beneficial
to the host. Furthermore, the term "agent" 100 may include an agent
belonging to the same family or a group, or an agent exhibiting a
common and/or a biological function.
[0032] The term "antibody" 104 as used herein, is used in the
broadest possible sense and may include but is not limited to an
antibody, a recombinant antibody, a genetically engineered
antibody, a chimeric antibody, a monospecific antibody, a
bispecific antibody, a multispecific antibody, a diabody, a
chimeric antibody, a humanized antibody, a human antibody, a
heteroantibody, a monoclonal antibody, a polyclonal antibody,
and/or an antibody fragment. The term "antibody" may also include
but is not limited to types of antibodies such as IgA, IgD, IgE,
IgG and/or IgM, and/or the subtypes IgG1, IgG2, IgG3, IgG4, IgA1
and/or IgA2. The term antibody may also include but is not limited
to an antibody fragments such as at least a portion of an intact
antibody 104, for instance, the antigen binding variable region.
Examples of antibody fragments include Fv, Fab, Fab', F(ab'),
F(ab').sub.2, Fv fragments, diabodies, linear antibodies
single-chain antibody molecules, multispecific antibodies, or other
antigen binding sequences of antibodies. Additional information may
be found in U.S. Pat. No. 5,641,870, U.S. Pat. No. 4,816,567, WO
93/11161, Holliger Et Al., Diabodies: Small Bivalent And Bispecific
Antibody Fragments, PNAS (Proc. Natl. Acad. Sci. USA), 90:
6444-6448 (1993), Zapata et al., Engineering Linear F(Ab')2
Fragments For Efficient Production In Escherichia Coli And Enhanced
Antiproliferative Activity, Protein Eng. 8(10): 1057-1062 (1995),
which are incorporated herein by reference. Antibodies may be
generated for therapeutic purposes by a variety of known
techniques, such as, for example, phage display, and/or transgenic
animals.
[0033] The term "heteroantibodies", as used herein, may include but
is not limited to, two or more antibodies, antibody fragments,
antibody derivatives, and/or antibodies with at least one
specificity linked together. Additional information may be found in
U.S. Pat. No. 6,071,517, which is incorporated herein by
reference.
[0034] The term "chimeric antibodies", as used herein, may include
but is not limited to antibodies having mouse variable regions
joined to human constant regions. In one aspect, "chimeric
antibodies" includes antibodies with human framework regions
combined with complementarity determining regions (CDR's) obtained
from a mouse and/or rat; those skilled in the art will appreciate
that CDR's may be obtained from other sources. Additional
information may be found in EPO Publication No 0239400, which is
incorporated herein by reference. Although the foregoing has
referred to the plural term "chimeric antibodies," those having
skill in the art will appreciate that the singular term "chimeric
antibody" may include but is not limited to singular instances of
examples given for the plural term, as appropriate to context (see,
e.g., the as-filed claims). The same is generally true for the use
of substantially any plural and/or singular terms as used herein;
that is, those having skill in the art can translate from the
plural to the singular and/or from the singular to the plural as is
appropriate to the context or application, and hence the various
singular/plural permutations are not expressly set forth herein for
sake of clarity.
[0035] The term "humanized antibody", as used herein, may include
but is not limited to an antibody having one or more human regions,
and/or a chimeric antibody with one or more human regions, also
considered the recipient antibody, combined with CDR's from a donor
mouse and/or rat immunoglobulin. In one aspect, humanized
antibodies may include residues not found in either donor or
recipient sequences. Humanized antibodies may have single and/or
multiple specificities. Additional information may be found in U.S.
Pat. No. 5,530,101, and U.S. Pat. No. 4,816,567, which are
incorporated herein by reference. Information may also be found in,
Jones et al., Replacing The Complementarity-Determining Regions In
A Human Antibody With Those From A Mouse, Nature,
321:522-525(1986); Riechmann et al., Reshaping Human Antibodies For
Therapy, Nature, 332:323-327 (1988); and Verhoeyen et al.,
Reshaping Human Antibodies: Grafting An Antilysozyme Activity,
Science, 239:1534 (1988), which are all incorporated herein by
reference.
[0036] The term "human antibodies", as used herein, may include but
is not limited to antibodies with variable and constant regions
derived from human germline immunoglobulin sequences. The term
human antibodies may include is not limited to amino acid residues
of non-human origin, encoded by non-human germline, such as, for
example, residues introduced by site directed mutations, random
mutations, and/or insertions. Methods for producing human
antibodies are known in the art and incorporated herein by
reference. Additional information may be found in U.S. Pat. No.
4,634,666, which is incorporated herein by reference.
[0037] The term "recombinant antibody", as used herein, may include
antibodies formed and/or created by recombinant technology,
including, but not limited to, chimeric, human, humanized, hetero
antibodies and the like.
[0038] The term "immune response component", as used herein, may
include, but is not limited to, at least a part of a macrophage, a
lymphocyte, a T-lymphocyte, a killer T-lymphocyte, an immune
response modulator, a helper T-lymphocyte, an antigen receptor, an
antigen presenting cell, a cytotoxic T-lymphocyte, a T-8
lymphocyte, a CD1 molecule, a B lymphocyte, an antibody, a
recombinant antibody, a genetically engineered antibody, a chimeric
antibody, a monospecific antibody, a bispecific antibody, a
multispecific. antibody, a diabody, a chimeric antibody, a
humanized antibody, a human antibody, a heteroantibody, a
monoclonal antibody, a polyclonal antibody, an antibody fragment,
and/or synthetic antibody.
[0039] Continuing to refer to FIG. 1, the epitope 102 or parts
thereof may be displayed by the agent 100, may be displayed on the
surface of the agent 100, extend from the surface of the agent 100,
and/or may only be partially accessible by the immune response
component. The term "epitope" 102, as used herein, may include, but
is not limited to, a sequence of at least 3 amino acids, a sequence
of at least nine nucleotides, an amino acid residue, a nucleotide,
a carbohydrate, a protein, a lipid, a capsid protein, a
polysaccharide, a lipopolysaccharide, a glycolipid, a glycoprotein,
and/or or at least a part of a cell. As used herein, the term
"epitope" 102 may be used interchangeably with antigen, paratope
binding site, antigenic determinant, and/or determinant. As used
herein, the term determinant can include an influencing or
determining element or factor, unless context indicates otherwise.
In one aspect the term "epitope" 102 includes, but is not limited
to, a peptide binding site. As used herein, the term "epitope" 102
may include structural and/or functionally similar sequences found
in the agent 100. The term "epitope" 102 includes, but is not
limited to, similar sequences observed in orthologs, paralogs,
homologs, isofunctional homologs, heterofunctional homologs,
heterospecific homologs, and/or pseudogenes of the agent 100.
[0040] In one aspect, the epitope 102 may be a linear determinant.
For example, the sequences may be adjacent to each other. In
another aspect, the epitope 102 is a non-linear determinant, for
example, including juxtaposed groups which are non-adjacent but
become adjacent to each other on protein folding. Furthermore, the
sequence of the non-linear determinant may be derived by
proteasomal processing and/or other mechanisms and the sequence
synthetically made for presentation to the immune response
component.
[0041] Continuing to refer to FIG. 1, in one aspect, the immune
system launches a humoral response producing antibodies capable of
recognizing and/or binding to the epitope 102 followed by the
subsequent lysis of the agent 100. Mechanisms by which the antigen
102 elicits an immune response are known in the art and such
mechanisms are incorporated herein by reference. In one aspect, the
binding of the antibody 104 to the epitope 102 to form an
antigen-antibody complex 105 is characterized as a lock and key
fit.
[0042] The epitope 102 may include any portion of the agent. In one
aspect, the epitope 102 may include at least a portion of a gene.
In another aspect the epitope may include at least a part of a
non-coding region.
[0043] In one aspect, the epitope 102 is capable of evoking an
immune response. The strength and/or type of the immune response
may vary, for example, the epitope 102 may invoke a weak response
and/or a medium response as measured by the strength of the immune
response. It is contemplated that in one instance the epitope 102
selected for targeting may be one that invokes a weak response in
the host, however, it may be selective to the agent 100. In another
example, the epitope 102 selected may invoke a weak response in the
host, however it may be selected for targeting as it is common to
agents deemed as targets. The herein described implementations are
merely exemplary and should be considered illustrative of like
and/or more general implementations within the ambit of those
having skill in the art in light of the teachings herein.
[0044] With reference to the figures, and with reference now to
FIG. 2 depicted is a diagrammatic view of one aspect of a method of
enhancing an immune system. In one aspect, an effective treatment
therapy towards a disease and/or a disorder may utilize one or more
immune response components designed to recognize one or more
antigens common to one or more agents. Such common antigens may
represent an effective target group of antigens. The immune
response components designed to seek out and neutralize the common
antigens may be effective against one or more agents.
[0045] With reference now to FIGS. 1 and 2, in one aspect, a shared
epitope 200 is depicted as common to three agents 206, 210 and 220.
In another aspect, a second shared epitope 212 is common to two
agents 206 and 210. In yet another aspect, a third shared epitope
218 is common to two agents 210 and 220. Finding a subset of common
epitopes shared amongst one or more agents may be done by
statistical analysis, for example, by metaprofiling. One variation
of this aspect is identification of at least one common epitope
shared with one or more agents also referred to as an antigenic
profile, and/or an antigenic signature. Additional information may
be found in a publication by Rhodes et al., Large Scale
Meta-Analysis Of Cancer Micorarray Data Identifies Common
Transcriptional Profiles Of Neoplastic Transformation And
Progression, PNAS Jun. 22, 2004, 101:(25) 9309-9314, and is
incorporated herein by reference.
[0046] Continuing to refer to FIGS. 1 and 2, in one aspect, one or
more agents 206, 210, and 220 depicted may share a subset of common
epitopes. The selection of epitopes may depend on a number of
criteria. For example, the initial selection may be based on,
including, but not limited to, the number of instances of
occurrences of the epitope 102 by one or more agents, the number of
instances of occurrence of the epitope 102 by the agent 100, the
location of the epitope 102, the size of the epitope 102, the
nature of the epitope 102, the sequence identity and/or homology of
the epitope 102 with host sequences, the composition of the epitope
102, and/or putative known or predicted changes in the epitope 102
sequence. The selection of epitopes may also depend on, for
example, the type of immune response component desired for treating
and/or managing the disease, disorder, and/or condition.
[0047] In one aspect, the epitope 102 selected has a probable
sequence match with an entity. The term "entity", as used herein,
may include the agent 100 and/or a host depending on context. For
example, whether the term entity includes the agent 100, the host,
or both will sometimes depend, for example, on the nature of a
described interaction. The term "host", as used herein, may include
but is not limited to an individual, a person, a patient, and/or
virtually anyone requiring management of a disease, disorder,
and/or condition. For example, the epitope 102 selected may have a
0-70% sequence match at the amino acid level with the entity, for
example, the host, or a 0-100% sequence match with the entity, for
example, the host or the agent 100. Those having skill in the art
will recognize that part of that context in relation to the term
"entity" is that generally what is desired is a practicably close
sequence match to the agent (e.g., HIV), so that the one or more
immune system components in use can attack it and a practicably
distant sequence match to the host (e.g., a patient), in order to
decrease or render less aggressive any attack by the immune system
components in use on the host. However, it is also to be understood
that in some contexts the agent will in fact constitute a part of
the host (e.g., when the agent to be eradicated is actually a
malfunctioning part of the host, such as in an auto-immune
disease), in which case that part of the host to be eradicated will
be treated as the "agent", and that part of the host to be left
relatively undisturbed will be treated as the "host." In another
aspect, the epitope 102 selected has a sequence match with the
entity, for example, a high sequence match, a relatively higher
sequence match with other agents compared to the host, or a 0-100%
sequence match with the agent 100. The term "sequence match", as
used herein, includes both sequence matching at the nucleic acid
level and/or at the protein level. In an embodiment, the epitope
102 selected has a low probable sequence match with the host. In
another embodiment, the epitope 102 selected has a high sequence
match with other agents.
[0048] In another aspect the epitope 102 selected has a likely
and/or a probable sequence match with other epitopes, for example,
including, but not limited to, the epitope 102 having a structural
sequence match, a functional sequence match, a similar functional
effect, a similar result in an assay and/or a combination.
Structural comparison algorithms and/or 3-dimensional protein
structure data may be used to determine whether two proteins may
have a structural sequence match. In another example the epitope
102 may have a functional match and/or share a similar functional
effect with epitopes of interest. In this example, the epitope 102
may have a lower probable sequence match but may still exert the
same functional effect. In another example, the epitope 102 and/or
other epitopes of interest may have a lower probable sequence match
but may share similar activities, for example, enzymatic activity
and/or receptor binding activity, as determined by using an
assay.
[0049] In another aspect the epitope 102 selected may be an
immunological effective determinant, for example, the epitope 102
may be weakly antigenic, however it may invoke an effective immune
response relating to, for example, the nature and/or the type of
the immune response component it invokes. In another aspect the
epitope 102 may exert a similar effect on the immune response, for
example, the epitope 102 selected may be part of the antigenic
structure of an agent unrelated to the disease or disorder in
question, however, it may exert a substantially similar effect on
the immune system as measured by, for example, the type, the
nature, or the period of the immune response.
[0050] In one aspect, a sequence match with an entity may be
determined by, for example, calculating the percent identity and/or
percent similarity between epitopes and/or between the epitope 100
and the host. In one aspect, the percent identity between two
sequences may be calculated by determining a number of
substantially similar positions obtained after aligning the
sequences and introducing gaps. For example, in one implementation
the percent identity between two sequences is treated as equal to
(=) a number of substantially similar positions/total number of
positions.times.100. In this example, the number and length of gaps
introduced to obtain optimal alignment of the sequences is
considered. In another aspect, the percent identity between two
sequences at the nucleic acid level may be determined by using a
publicly available software tool such as BLAST, BLAST-2, ALIGN
and/or DNASTAR software. Similarly, the percent identity between
two sequences at the amino acid level may be calculating by using
publicly available software tools such as, for example,
Peptidecutter, AACompSim, Find Mod, GlycoMod, InterProtScan, DALI
and/or tools listed on the ExPasy (Expert Protein Analysis System)
Proteomics Server at http://www.expasy.org/. In one embodiment, the
percent identity at the nucleic acid level and at the amino acid
level are determined.
[0051] It will be appreciated by those skilled in the art that the
epitope 102 selected need not be limited to a matching sequence
displayed by the agent 100. In one aspect, a meta signature and/or
a consensus sequence may be derived based on any number of
criteria. In one aspect, the meta signature may be derived by
analysis of data from sources such as, for example, antigenic
evolution, genetic evolution, antigenic shift, antigenic drift,
data from crystal structure, probable match with a host, probable
match with other strains, and/or strength of the immunogenic
response desired. The meta signature may include new sequences
and/or may exclude some sequences. For example, it may include
silent mutations, mismatches, a spacer to bypass a hotspot or a
highly mutagenic site, predicted changes in the sequence, and/or
may include epitopes from multiple agents thus providing protection
from multiple agents. As another example, the meta signature may
exclude sequences, such as, for example, including, but not limited
to, mutagenic sequences and/or sequences with a match to the
host.
[0052] In one aspect, the predicted changes in the epitope 102 may
be determined by analysis of past variations observed and/or
predicted in the agent 100 (e.g., FIG. 1). Computational analysis
can be used to determine regions showing sequence variations and/or
hot spots. In one aspect, high speed serial passaging may be
performed computationally mimicking the serial passaging that
occurs naturally with a production of a new strain of the agent
100. It will be appreciated by those of skill in the art that the
hot spots need not be identified by examining the epitope 102,
and/or by examining the epitope 102 in context with the agent 100.
Information pertaining to hot spots can also be extrapolated by
performing sequence analysis of other agents and/or domain analysis
of the other agents. For example, in one implementation the epitope
102 may be part of a domain shared between multiple agents which
may lack the epitope 102 of interest. Information pertaining to
hotspots identified in the domain of the other agents may be of
practical use in determining the metasignature.
[0053] In one aspect, one or more sets and/or subsets of epitopes
may be formed. The nature and type of criteria used to form the
sets and/or subsets will depend, for example, on the nature and
type of the agent 100, the duration of the immune response desired
(e.g., short-term immunity, or long-term immunity), the nature of
the immune response desired (e.g., weak, moderate, or strong), the
population seeking protection (e.g., presence of prior exposure)
and the like. The sets and subsets so formed may accept input
either robotically or from a user (e.g., a manufacturer of immune
response components, wet lab, or medical personnel).
[0054] The pattern changes predicted in the epitope 102 may be
supplemented, for example, by other methodology, statistical
analysis, historical data, and other extrapolations of the type
utilized by those having skill in the art. The knowledge of these
predicted pattern changes represents an arsenal in the design
and/or selection of the immune response components. The predicted
pattern changes may be used to determine the progression of the
changes in the immune response component required to manage such
changes. Inferring the pattern changes in the epitope 102 and using
the information to modulate the progressing response may help
manage the response more effectively. For example, the pattern
changes may be used to provide a timeline of when the therapy could
be changed, what therapy should constitute the change, or the
duration of the change. As a more specific example, one reason why
Human Immunodeficiency Virus (HIV) is able to successfully kill its
host is that the virus mutates faster than the immune system can
track and respond to its mutations. In a specific implementation of
the subject matter described herein, a sample of HIV is taken from
a patient at a point in time and computational biological
techniques are used to infer likely mutations of the virus at
future times. Cloning techniques are then utilized to synthesize
immune system activating aspects of the future HIV strains, and
thereafter subsequent cloning techniques are utilized to rapidly
generate copious amounts of one or more immune system components
(e.g., antibodies) that are keyed to the likely future generation
of the patient's HIV. Once cloned, the immune system components are
then loaded back to the patient and thus are present and waiting
for the HIV when it mutates. If the HIV mutates as anticipated, the
preloaded immune response components attack the mutated HIV,
thereby likely greatly reducing the presence of the HIV. In another
implementation, the actual mutation of the HIV is manually tracked,
and once the actual mutation has been determined, yet more cloning
techniques are utilized to generate yet more immune system
components appropriate to the mutated virus.
[0055] In one aspect, the epitope 102 selected for designating the
immune response component may be synthetically made and/or derived
from the agent 100. In one embodiment the epitope 102 selected is
derived from an agent 100 extracted from an individual desiring
treatment and/or an individual found resistant to that agent. In
one aspect the epitope 102 selected for designating the immune
response component may include multiple copies of the exact same
epitope and/or multiple copies of different epitopes.
[0056] In one aspect the metasignature includes sequences matching
adjacent and/or contiguous sequences. In another aspect the
metasignature includes non adjacent sequences. For example, it will
be appreciated by those of skill in the art that peptide splicing
and/or proteosomal processing of the epitope 102 that occurs
naturally may result in the formation of a new epitope, for
example, a non-linear epitope. In this example, proteosomal
processing may result in the excision of sequences transposing
non-contiguous sequences to form the non-linear epitope. Additional
information may be found in Hanada et al., Immune Recognition Of A
Human Renal Cancer Antigen Through Post-Translational Protein
Splicing, Nature 427:252 (2004), and Vigneron et al., An Antigenic
Peptide Produced By Peptide Splicing In The Proteasome, Science
304:587 (2004) hereby incorporated by reference herein in its
entirety.
[0057] Additionally, it will also be appreciated by those of skill
in the art that the metasignature may include sequences displayed
on two different parts of the agent 100. For example, non adjacent
sequences may appear adjacent each other when the protein is
folded. In this aspect, the metasignature may include the
nonadjacent sequences for identifying the metasignature.
Furthermore, the metasignature may include nonadjacent sequences
corresponding to a specific conformational state of a protein.
Immune response components designed to bind such sequences may be
specific to the conformational state of the protein. 3-D and/or
crystal structure information may also be used to designate the
metasignature.
[0058] In one aspect, the metasignature may include multiple sets
of epitopes targeting a predicted pattern change and/or an observed
pattern change. For example, multiple sets of epitopes may be
designed for vaccination and/or for production of immune response
components.
[0059] Techniques for epitope mapping are known in the art and
herein incorporated by reference. For example, FACS analysis and
ELISA may be used to investigate the binding of antibodies to
synthetic peptides including at least a portion of the epitope.
Epitope mapping analysis techniques, Scatchard analysis and the
like may be used to predict the ability of the antibody 104 to bind
to the epitope 102 presented on the agent 100, to determine the
binding affinity of the antibody 104 to the epitope 102, and/or to
discern a desirable configuration for the antibody 104.
[0060] Continuing to refer to FIG. 2, in one aspect, for example,
the sequences of selected epitopes 200, 212, and 218 may be used to
design one or more complementary antibodies 224, 222, and 226,
respectively. Techniques for making antibodies are known in the art
and are incorporated herein by reference. The purified
complementary antibodies 230, 228, or 232 may then be made
available for therapeutic and/or prophylactic treatment.
[0061] The term "an effective treatment therapy", as used herein,
includes, but is not limited to, the use of immune response
components in combination with other antibodies, antibody
fragments, and/or in combination with other treatments, including,
but not limited to, drugs, vitamins, hormones, medicinal agents,
pharmaceutical compositions and/or other therapeutic and/or
prophylactic combinations. In another aspect, the immune response
component may be used in combination, for example, with a modulator
of an immune response and/or a modulator of an antibody. In one
aspect, cocktails of immune response components may be
administered, for example, by injecting by a sub-cutaneous, nasal,
intranasal, intramuscular, intravenous, intraarterial, intrathecal,
intracapsular, intraorbital, intracardiac, transdermal,
intradermal, intraperitoneal, transtracheal, subcuticular,
intraarticular, subcapsular, subarachnoidal, intraspinal, epidural,
intrasternal, infusion, topical, sublingual, and/or enteric
route.
[0062] The therapeutic effect of the immune response component may
be produced by one or more modes of action. For example, in one
aspect, the immune response component may produce a therapeutic
effect and/or alleviate the symptoms by targeting specific cells
and neutralizing them. In another aspect, the immune response
component may bind to and/or block receptors present on the agent
100 and/or may directly and/or indirectly block the binding of
molecules, such as, for example, cytokines, and/or growth factors,
to the agent 100. In another aspect, the therapeutic effect of the
immune response component is produced by functioning as signaling
molecules. In this example, the immune response component may
induce cross linking of receptors with subsequent induction of
programmed cell death.
[0063] The immune response component may be engineered to include,
for example, one or more effector molecules, such as, for example,
drugs, small molecules, enzymes, toxins, radionuclides, cytokines,
and/or DNA molecules. In this example, the immune response
component may serve as a vehicle for targeting and binding the
agent 100 and/or delivering the one or more effector molecules. In
one aspect, the immune response component may be engineered to
include the one or more effector molecules without the natural
effector functions of the immune response component.
[0064] In another aspect, one or more immune response components
may be coupled to molecules for promoting immune system cells to
eliminate unwanted cells. This technique has been described for the
treatment of tumors, viral infected cells, fungi, and bacteria
using antibodies. Additional information may be found in U.S. Pat.
No. 4,676,980 to Segal, which is incorporated herein by
reference.
[0065] The criteria for selection of the one or more immune
response components may vary, for example, one criterion may
include the strength of the interaction or the binding affinity of
the immune response component for the antigen 102. Numerous
techniques exist for enhancing the binding affinity of the antibody
for the antigen 102. In one aspect, the binding affinity of the
antibody for the antigen 102 may be enhanced by constructing phage
display libraries from an individual who has been immunized with
the antigen 102 either by happenstance or by immunization. The
generation and selection of higher affinity antibodies may also be
improved, for example, by mimicking somatic hypermutagenesis,
complementarity-determining region (CDR) walking mutagenesis,
antibody chain shuffling, and/or technologies such as Xenomax
technology (available from Abgenix, Inc. currently having corporate
headquarters in Fremont, Calif. 94555). In one example, antibodies
including introduced mutations may be displayed on the surface of
filamentous bacteriophage. Processes mimicking the primary and/or
secondary immune response may then be used to select the desired
antibodies, for example, antibodies displaying a higher binding
affinity for the antigen and/or by the evaluating the kinetics of
dissociation. For additional information see, Low et al., Mimicking
Somatic Hypermutation: Affinity Maturation Of Antibodies Displayed
On Bacteriophage Using A Bacterial Mutator Strain, J. Mol. Biol.
260:359-368 (1996); Hawkins et al. Selection Of Phage Antibodies By
Binding Affinity. Mimicking Affinity Maturation, J. Mol. Biol.
226:889-896 (1992), which are incorporated herein by reference.
[0066] In another example, the generation and/or selection of
higher affinity antibodies may be carried out by CDR walking
mutagenesis, which mimics the tertiary immune selection process.
For example, saturation mutagenesis of the CDR's of the antibody
104 may be used to generate one or more libraries of antibody
fragments which are displayed on the surface of filamentous
bacteriophage followed by the subsequent selection of the relevant
antibody using immobilized antigen. Sequential and parallel
optimization strategies may be used to then select the higher
affinity antibody. For additional information see Yang et al., CDR
Walking Mutagenesis For The Affinity Maturation Of A Potent Human
Anti-HIV-1 Antibody Into The Picomolar Range, J. Mol. Biol
254(3):392-403 (1995), which is incorporated herein by reference in
its entirety.
[0067] In yet another example, site directed mutagenesis may be
used to generate and select higher affinity antibodies, for
example, by parsimonious mutagenesis. In this example, a computer
based method is used to identify and screen amino acids included in
the one or more CDR's of a variable region of an antibody 104
involved in an antigen-antibody binding. Additionally, in some
implementations, the number of codons introduced is such that about
50% of the codons in the degenerate position are wildtype. In
another example, antibody chain shuffling may be used to generate
and select higher affinity antibodies. These techniques are known
in the art and are herein incorporated by reference.
[0068] The dosage of the immune response component may vary and in
one aspect may depend, for example, on the duration of the
treatment, body mass, severity of the disease, and/or age.
Compositions including immune response components may be delivered
to an individual for prophylactic and/or therapeutic treatments. In
one aspect, an individual having a disease and/or condition is
administered a treatment dose to alleviate and/or at least
partially cure the symptoms. In this example, a therapeutically
effective dose is administered to the patient.
[0069] In another aspect, an individual's resistance may be
enhanced by providing a prophylactically measured dose. For
example, including, but not limited to, the individual may be
genetically vulnerable to the disease and/or condition, the
individual may visit a location where the agent 100 is prevalent,
or the individual may fear exposure to the agents and/or related
agents associated with the disease and/or condition.
[0070] Optimization of the physico-chemical properties of the
immune response component may be improved, for example, by computer
based screening methods. Properties affecting antibody therapeutics
may be improved, such as, for example, stability, antigen binding
affinity, and/or solubility. Additional information may be found in
US Patent Application number 20040110226 to Lazar, which is
incorporated herein by reference.
[0071] With reference to the figures, and with reference now to
FIGS. 1, 2, and 3, depicted is one aspect of the antigen antibody
interaction 105 showing the occurrence of mutational changes in the
selected epitope 200 and corresponding changes in the complementary
antibody 224. Such mutational changes in the epitope 200, for
example, may be minor or major in nature. These minor and/or major
antigenic variations may render an existing treatment less
effective. Thus an effective treatment therapy towards a disease or
disorder may include treating the disease or disorder with one or
more antibodies designed to anticipate one or more antigenic
variations common to one or more agents 100 or one or more related
agents. Furthermore, predicting the course of the minor and/or
major antigenic variations of the agent 100 and/or the related
agents would also be beneficial in designing or selecting the one
or more antibodies. Additionally, in some implementations the
inclusion of information from SNP databases is helpful in designing
antibodies for binding the selected epitope 200.
[0072] Minor changes in the epitope 102 which do not always lead to
the formation of a new subtype may be caused, for example, by point
mutations in the selected epitope 200. In one aspect, the
occurrence of point mutations may be localized, for example, to
hotspots of the selected epitope 200. The frequency and/or
occurrence of such hotspots may be provided by the computer based
method. Additionally, the method provides for access to databases
including, for example, historical lists of the antigenic
variations of the agent 100 and/or of the selected epitope 200, for
example, from previous endemics and/or pandemics. Such information
may be part of an epitope profile for charting the progression of
the immune response. For example, including, but not limited to, a
point mutation in the glutamic acid at position 92 of the NS1
protein of the influenza virus has been shown to dramatically
downregulate activation of cytokines. Such information may be
useful in designating the metasignature.
[0073] Continuing to refer to FIGS. 1, 2, and 3, depicted is that a
mutation 310 in the selected epitope 200 results in a mutated
epitope 302. The term "the selected epitope 200" as typically used
herein, often constitutes a type of the more general term of
presented epitope, unless context indicates otherwise. The
generation of the mutated epitope 302 may reduce the binding of the
immune response component, for example, the antibody 224. In one
aspect, effective binding could be enhanced by generating a new
antibody 324 corresponding to the mutated epitope 302. The
frequency of minor antigenic variations may be predicted by
examining known and/or predicted hotspots. For example, additional
mutations 311 and/or 314 may be predicted by the computer based
method and corresponding antibodies 328 and/or 326 respectively,
designed to factor such antigenic variations in the mutated
epitopes 306 and/or 304, respectively. In one aspect, an effective
treatment therapy, may incorporate this knowledge in providing an
effective humoral response towards an agent 100. For example, a
cocktail of immune response components may include the antibodies
224, 324, 326, 328 for binding to the selected epitope 200 and/or
its predicted mutated versions. In one aspect, the cocktail of one
or more antibodies may be supplemented by additional chemicals,
growth factors, drugs, or growth factors. In another aspect, the
effective treatment therapy may include varying doses of immune
response components, for example, a substantially larger dosage of
326 relative to 324, 328, and/or 224.
[0074] Referring now to FIG. 4, for example, one or more new
epitopes 402, 404, 406, and/or 408 may appear on the surface of the
agent 100. In one aspect, major changes may occur in the antigenic
variants present on the surface of the agent 100 resulting in the
formation of a new subtype. The appearance of new epitopes
observed, for example, may occur as a result of antigenic shifts,
reassortment, reshuffling, rearrangement of segments, and/or
swapping of segments and generally marks the appearance of a new
virulent strain of the agent 100. In one instance the prediction of
the new epitopes may mark the emergence of a new strain, a new
subtype, and/or the reemergence of an older strain. In this
instance, natural and/or artificial humoral protection in an
individual does not provide adequate protection.
[0075] Generally, when major changes do occur a larger section of
the population succumbs to the infection leading to a pandemic. The
problem may be alleviated in part, for example, by predicting the
appearance of new strains and/or subtypes as a result of the
appearance of new epitopes and/or the disappearance of existing
epitopes. In one aspect, for example, including, but not limited
to, the prediction of the new epitopes may be directed towards a
subset of genes, for example, important for virulence and/or
replication of the agent 100. For example, examining the appearance
of new subtypes of influenza virus type A shows that the antigenic
variations occur for the most part in the neuraminidase and/or
hemagglutinin gene.
[0076] In another aspect, the selected epitope 200 may steer clear
of highly variable regions and focus instead on areas of lower
probability of mutations. Thus epitopes selected may circumvent
hotspots of antigenic variations and target other specific regions
of an agent 100, such as, for example, the receptor binding site on
the surface of the agent 100. In another example, the selected
epitope 200 may not be readily accessible to the immune response
component, for example, the receptor binding site may be buried
deep in a pocket and may be surrounded by readily accessible
sequences exhibiting a higher level of antigenic variations. In
this example, one possibility may include providing small antibody
fragments that penetrate the receptor binding site preventing the
agent 100 from binding its target. In another example, a drug
and/or chemical may be used to exaggerate the accessibility of the
receptor binding site. In yet another example, a chemical with a
tag may be used to bind to the residue and the tag used for biding
the immune response component.
[0077] In another aspect, the immune response component may be so
designed so as to circumvent the shape changes in the epitope 102
and provide minimally effective binding to the epitope 102. In this
example the antibody designed may include accommodations to its
design by the prediction of hotspots and/or the mutational changes
in the epitope 102.
[0078] In one aspect the size of the immune response component may
be manipulated. For example, an immune response component, for
example, the antibody 104 may be designed to include the
practicably minimal binding site required to bind the epitope 102.
In another example, the immune response component may be designed
to the smallest effective determinant.
[0079] In one aspect, an effective treatment therapy towards a
disease and/or disorder may include one or more immune response
components designed to anticipate and/or treat an antigenic drift
and/or an antigenic shift predicted for multiple agents. The agents
need not be related to each other, for example, the therapy might
be designed for an individual suffering from multiple diseases.
[0080] Following are a series of flowcharts depicting an
illustrative environment for the implementation of processes. For
ease of understanding, the flowcharts are organized such that the
initial flowcharts present implementations via an overall "big
picture" viewpoint and thereafter the following flowcharts present
alternate illustrative environments and/or expansions of the "big
picture" flowcharts as either sub-steps or additional steps
building on one or more earlier-presented flowcharts. Those having
skill in the art will appreciate that the style of presentation
utilized herein (e.g., beginning with a presentation of a
flowchart(s) presenting an overall view and thereafter providing
additions to and/or further details in subsequent flowcharts)
generally allows for a rapid and easy understanding of the various
illustrative environments.
[0081] With reference now to FIG. 14, depicted is a partial view of
a system that may serve as an illustrative environment of and/or
for subject matter technologies. In one aspect the environment
depicted includes a computer system 1400 including a computer
program 1402. Depicted is the computer program 1402 including
instructions 1403, 1404, and/or 1405. The computer program 1402 may
include a first set of instructions for designating one or more
epitopes of at least one agent 1403. The computer program 1402 may
include a second set of instructions for predicting changes in the
one or more epitopes of the at least one agent 1403. The computer
program 1402 may include a third set of instructions for aiding the
identification of one or more immune response components associated
with the one or more epitopes of the at least one agent 1404. In
one exemplary implementation of the system, depicted is a user 1410
(e.g., a medical professional, a researcher, a scientist, a
patient, a technician, a manufacturer, a drug maker or the like)
employing the system. In another exemplary implementation of the
system, the computer program 1402 has access to a database 1406. In
one exemplary implementation a feedback loop is set up between the
computer program and the database 1406. The output 1407 may be fed
back into the computer program 1402 and/or displayed on the
computer system 1400. The system may be used as a research tool, as
a tool for furthering treatment or the like.
[0082] With reference now to FIG. 15, depicted is a partial view of
a system that may serve as an illustrative environment of and/or
for subject matter technologies. The user 1410 may input data 1500,
for example, to affect the output 1407. Robotic or user input of
data may also be provided via a medical system 1504, a
manufacturing system 1505, or a wet lab system 1506 and the output
1407 fed back into the computer program 1402 and/or displayed on
the computer system 1400.
[0083] B. Operation(s) and/or Process(es)
[0084] Following are a series of flowcharts depicting
implementations of processes. For ease of understanding, the
flowcharts are organized such that the initial flowcharts present
implementations via an overall "big picture" viewpoint and
thereafter the following flowcharts present alternate
implementations and/or expansions of the "big picture" flowcharts
as either sub-steps or additional steps building on one or more
earlier-presented flowcharts. Those having skill in the art will
appreciate that the style of presentation utilized herein (e.g.,
beginning with a presentation of a flowchart(s) presenting an
overall view and thereafter providing additions to and/or further
details in subsequent flowcharts) generally allows for a rapid and
easy understanding of the various process implementations.
[0085] Several of the alternate process implementations are set
forth herein by context. For example, as set forth herein in
relation to FIG. 5, what is described as method step 504 is
illustrated as a list of exemplary qualifications of an agent.
Those skilled in the art will appreciate that when what is
described as method step 504 is read in the context of what are
described as method step 503 and method step 502, it is apparent
that the list of exemplary qualifications of the agent, in context,
is actually illustrative of an alternate implementation of method
step 502 of presenting at least a portion of at least one of a
virus, a bacterium, a yeast, a mold, a fungus, a mycoplasma, a
ureaplasma, a Chlamydia, a rickettsia, a nanobacterium, a prion, an
agent responsible for TSE, a multicellular parasite, a protein, an
infectious protein, a nucleic acid, a metabolic by-product, a
cellular by-product, or a toxin. Likewise, when what is described
as method step 505 is read in the context of what are described as
method step 503 and method step 502, it is apparent that, in
context, method step 505 is actually illustrative of an alternate
implementation of method step 502 of presenting at least a portion
of a living agent. Likewise again, when what is described as method
step 505 is read in the context of what are described as method
step 503 and method step 502, it is apparent that, in context,
method step 505 is actually illustrative of an alternate
implementation of method step 502 of presenting at least a portion
of a non-living agent. Contextual readings such as those just set
forth in relation to method steps 504, 505, and 506 are within the
ambit of one having skill in the art in light of the teaching
herein, and hence are not set forth verbatim elsewhere herein for
sake of clarity.
[0086] With reference now to FIG. 5, depicted are high level logic
flow charts of various alternate process implementations. Method
step 500 shows the start of the process. Method step 502 shows the
presentation of one or more determinants. Depicted is that in
various alternate implementations, method step 502 includes steps
503 and/or 510. Illustrated is that in various alternate
implementations, method step 503 includes substeps 504, 505, and/or
506. Method step 503 depicts some exemplary qualifications of an
agent. As depicted method step 504 may include at least a portion
of at least one of a virus, a bacterium, a yeast, a mold, a fungus,
a mycoplasma, a ureaplasma, a Chlamydia, a rickettsia, a
nanobacterium, a prion, an agent responsible for TSE, a
multicellular parasite, a protein, an infectious protein, a nucleic
acid, a metabolic by-product, a cellular by-product, and/or a
toxin. The agent may include a living agent method step 504 and/or
a non-living agent 506 of an agent. Method step 510 depicts the one
or more determinants and includes additional steps 511, 512, and/or
513. Method step 511 depicts including the one or more determinants
wherein the one or more determinants include at least a part of at
least one of an amino acid residue, a nucleotide, a carbohydrate, a
protein, a lipid, a capsid protein, a polysaccharide, a
lipopolysaccharide, a glycolipid, or a glycoprotein. Method step
512 depicts wherein the one or more determinants may include
substantially linear determinants. Method step 513 depicts wherein
the one or more determinants may include non-linear determinants.
It will also be appreciated by those skilled in the art that method
step 500 may include accepting input related to, for example, the
agent, the one or more determinants and/or other relevant criteria
such as a size of the determinant, a type of the determinant, a
nature of the disease, a disorder and/or a condition requiring
management, and/or a sensitivity of a group requiring management.
Method step 530 depicts providing a predicted pattern for the
progression related to the one or more determinants of the agent.
For example, previous pattern changes known and/or predicted may be
used to extrapolate future progressions of the pattern changes that
may be observed in the one or more determinants of the agent.
Method step 560 depicts designating the selection of at least one
immune response component corresponding to the one or more
determinants of the agent. The immune response components so
designated may include those for managing a disease, a condition or
for managing a response, for example. Method step 590 shows the end
of the process.
[0087] With reference now to FIG. 6, depicted is a high-level logic
flowchart depicting alternate implementations of the high-level
logic flowchart of FIG. 5. Depicted is that method step 560
includes method step 603, 604, 605, and/or 606. Method step 603
depicts designating at least one immune response component, such
as, for example, including but not limited to, of at least a part
of one or more of a macrophage, a lymphocyte, a T-lymphocyte, a
killer T-lymphocyte, an immune response modulator, a helper
T-lymphocyte, an antigen receptor, an antigen presenting cell, a
cytotoxic T-lymphocyte, a T-8 lymphocyte, or a cluster
differentiation molecule such as a CD3 and/or a CD1 molecule.
Method step 604 shows designating at least one immune response
component, such as, for example, including but not limited to, at
least one modulator of at least a part of at least one of a
macrophage, lymphocyte, a T-lymphocyte, a killer T-lymphocyte, an
immune response modulator, a helper T-lymphocyte, an antigen
receptor, an antigen presenting cell, a cytotoxic T-lymphocyte, a
T-8 lymphocyte, a cluster differentiation molecule, a CD3 molecule
and/or a CD1 molecule. Method step 605 shows designating at least
one immune response component, such as, for example, at least a
part of at least one of a B-lymphocyte. Method step 606 shows
designating at least one immune response component, for example, at
least one of a modulator of at least a part of a B-lymphocyte.
[0088] Referring now to FIG. 7, depicted is a high-level logic
flowchart depicting alternate implementations of the high-level
logic flowchart of FIG. 5. Depicted is that in various alternate
implementations method step 560 includes method step 703, 704,
and/or 705. Method step 703 shows designating at least one immune
response component, for example, at least a part of at least one of
an antibody, a recombinant antibody, a genetically engineered
antibody, a chimeric antibody, a monospecific antibody, a
bispecific antibody, a multispecific antibody, a diabody, a
chimeric antibody, a humanized antibody, a human antibody, a
heteroantibody, a monoclonal antibody, a polyclonal antibody,
and/or an antibody fragment. Method step 704 depicts designating at
least one immune response component, for example, at least one
modulator of at least a part of at least one of an antibody, a
recombinant antibody, a genetically engineered antibody, a chimeric
antibody, a monospecific antibody, a bispecific antibody, a
multispecific antibody, a diabody, a chimeric antibody, a humanized
antibody, a human antibody, a heteroantibody, a monoclonal
antibody, polyclonal antibody, and/or an antibody fragment. Method
step 705 illustrates designating at least one immune response
component e.g., at least a part of at least one of a synthetic
antibody or a modulator of a synthetic antibody.
[0089] Referring now to FIG. 8, depicted is a high-level logic
flowchart depicting alternate implementations of the high-level
logic flowchart of FIG. 5. In one alternate implementation, as
depicted in FIG. 8, method step 502 includes method steps 800, 810,
811, and/or 812. Method step 800 depicts including data from
databases for influencing the selection of the one or more
determinants of the agent. Method step 800 also includes additional
steps 803, 804 and/or 805. Method step 803 depicts including at
least one of a plant database, an animal database, a bacterium
database, a viral database, a biological database, a genetic
database, a genomic database, a structural database, a SNP
database, or an immunological database. Method step 804 and 805
depicts including a human database or a pathogen database,
respectively, for influencing the selection of the one or more
determinants.
[0090] Continuing to refer to FIG. 8, method step 810 shows
influencing the presentation of the one or more determinants of the
agent by including information from one or more databases having
information related to a restriction fragment length polymorphism,
a microsatellite marker, a short tandem repeat, a random amplified
polymorphic DNA, an amplified fragment length polymorphism, or a
sequence repeat. Method step 811 depicts presenting one or more
determinants of an agent associating with a response and wherein
the response requires management (e.g., a biological response).
Method step 812 depicts presenting one or more determinants of an
agent associated with eliciting at least a part of at least one of
an immune response or a progression of an immune response.
[0091] With reference now to FIG. 9, depicted is a high-level logic
flowchart depicting alternate implementations of the high-level
logic flowchart of FIG. 5. In one alternate implementation, as
depicted in FIG. 9, method step 530 includes method steps 900.
Method step 900 depicts forming a set or a subset (e.g., a group of
one or more determinants). The set or subset may be formed in
response to an input method step 902 (e.g., biological criteria,
geographical criteria or other substantive criteria), in response
to a robotic input method step 903 and/or in response to a user
input method step 904.
[0092] With reference now to FIG. 10, depicted is a high-level
logic flowchart depicting alternate implementations of the
high-level logic flowchart of FIG. 5. Shown is one alternate
implementation, method step 530 includes method steps 1000-1018.
The criteria used to form sets or subsets may include at least one
determinant with up to about 80% amino acid sequence match with an
entity method step 1001. Method step 1002 depicts forming set or
subsets by including at least one determinant with up to about 60%
amino acid sequence match with an entity. Method step 1003 depicts
forming set or subsets by including at least one determinant having
at least 88% sequence match with an entity and/or at least a 75%
sequence match with an entity. Method step 1004 depicts forming set
or subsets by including at least one determinant having a likely
sequence match with an entity. Method step 1005 depicts forming set
or subsets by including at least one determinant with up to about
70% amino acid sequence match with an entity. Method step 1006
depicts forming set or subsets by including at least one
determinant with up to about 0-80% amino acid sequence match with
an entity. Method step 1007 depicts forming set or subsets by
including at least one determinant having between 0 to 100%
sequence match with an entity. Method step 1008 depicts forming set
or subsets by including at least one determinant having a
substantially similar structural match with an entity. Method step
1009 depicts forming set or subsets by including at least one
determinant having a copy number of at least two and that is
recognized (e.g., by the occurrence of an immune response directed
towards the one or more determinants).
[0093] Continuing to refer to FIG. 10, method step 1010 depicts
forming set or subsets by including at least one determinant having
a substantially similar functional effect. Method step 1011 depicts
forming set or subsets by including al least one substantially
antigenic determinant. Method step 1012 depicts forming set or
subsets by including at least one determinant displayed by the
agent (e.g., on the surface of the agent). Method step 1013 depicts
forming set or subsets by including at least one determinant having
a substantially similar functional sequence match with an entity.
Method step 1014 depicts forming set or subsets by including at
least one determinant having a substantially similar effect on the
immune response. Method step 1015 depicts forming set or subsets by
including at least one determinant having a substantially similar
result in an assay. Method step 1016 depicts forming set or subsets
by including at least one immunologically effective determinant.
Method step 1017 depicts forming set or subsets by including at
least one determinant having a copy number of at least two and
displayed by the agent. Method step 1018 depicts forming set or
subsets by including at least one determinant bound by the agent
(e.g., a cofactor, or an ectopic determinant that may be part of
the agent or not part of the agent).
[0094] With reference now to FIG. 11, depicted is a high-level
logic flowchart depicting alternate implementations of the
high-level logic flowchart of FIG. 5. Depicted is that method step
530 includes method step 1102 and/or 1103. Method step 1102 shows
associating the one or more determinants of the agent with a
predicted pattern for a progression of at least a part of an immune
response in a host. Method step 1103 shows predicting one or more
pattern changes in the one or more determinants of the agent.
Method step 1103 includes method step 1104 which depicts
correlating the one or more pattern changes in the one or more
determinants of the agent to one or more progressions of an
elicited immune response.
[0095] Referring now to FIG. 12, depicted is a high-level logic
flowchart depicting alternate implementations of the high-level
logic flowchart of FIG. 5. Depicted is that method step 560
includes method step 1202-1210. Method step 1202 shows including
data from at least one of a plant database, an animal database, a
bacterium database, a viral database, a biological database, a
genetic database, a genomic database, a structural database, a SNP
database, or an immunological database. Method step 1203 shows
including data from databases for influencing the identification of
the one or more determinants of the agent. Method step 1204 shows
including data from a human database. Method step 1205 shows
including data from a pathogen database. Method step 1206 shows
including designating the selection of at least one immune response
component corresponding to the one or more determinants of the
agent associated with the at least one determinant of the agent
operable for modulating at least a part of the immune response.
Method step 1207 shows including directing the formation of one or
more human or humanized antibodies associated with the one or more
determinants of the agent operable for modulating at least a part
of the immune response. Method step 1208 shows including directing
the formation of one or more chimeric antibodies associated with
the one or more determinants of the agent operable for modulating
at least a part of the immune response. Method step 1209 shows
including directing the formation of one or more recombinant
antibodies associated with the one or more determinants of the
agent operable for modulating at least a part of the immune
response. Method step 1210 shows including directing the formation
of one or more recombinant antibodies associated with the one or
more determinants of the agent operable for modulating at least a
part of the immune response.
[0096] With reference now to FIG. 13, depicted is a high-level
logic flowchart depicting alternate implementations of the
high-level logic flowchart of FIG. 5. Depicted is that method step
560 includes method step 1302. Method step 1302 includes aiding the
selection of the at least one immune response component by
providing a plan (e.g., a scheme, a list of options, or a course of
action). What is shown is that method step 1302 includes additional
method step 1303 and/or 1304. Method step 1303 includes providing
the plan for managing at least a part of the immune response.
Method step 1304 includes wherein the plan is e.g., at least one of
a dosage, a dosing pattern, an effective route, or duration of a
dosage. Method step 1304 includes additional method step 1305
wherein the effective route is e.g., at least one of a
sub-cutaneous route, a nasal route, an intranasal route, an
intramuscular route, an intravenous route, an intraarterial route,
an intrathecal route, an intracapsular route, an intraorbital
route, an intracardiac route, a transdermal route, an intradermal
route, an intraperitoneal route, a transtracheal route, a
subcuticular route, an intraarticular route, a subcapsular route, a
subarachnoidal route, an intraspinal route, an epidural route, an
intrasternal route, an infusion route, a topical route, a
sublingual route, or an enteric route.
[0097] C. Variation(s), and/or Implementation(s)
[0098] Those having skill in the art will recognize that the
present application teaches modifications of the devices,
structures, and/or processes within the spirit of the teaching
herein. For example, in one aspect, the immune response components
may be formulated to cross the blood-brain barrier which is known
to exclude mostly hydrophilic compounds. For example, an antibody
fragment may be encased in a lipid vesicle. In another example, the
antibody or a portion of the antibody may be tagged onto a carrier
protein or molecule. In another example, an antibody may be split
into one or more complementary fragments, each fragment encased by
a lipid vesicle, and each fragment functional only on binding its
complementary fragment. Once the blood-brain barrier has been
crossed the lipid vesicle may be dissolved to release the antibody
fragments which reunite with their complementary counterparts and
form a fully functional antibody. Other modifications of the
subject matter herein will be appreciated by one of skill in the
art in light of the teachings herein.
[0099] Those having skill in the art will recognize that the
present application teaches modifications of the devices,
structures, and/or processes within the spirit of the teaching
herein. For example, in one aspect the immune response components
may be made in large format. The method lends itself to both small
format or personalized care applications and large scale
applications. Other modifications of the subject matter herein will
be appreciated by one of skill in the art in light of the teachings
herein.
[0100] Those having skill in the art will recognize that the
present application teaches modifications of the devices,
structures, and/or processes within the spirit of the teaching
herein. For example, in one aspect, the method may be used to
designate immune response components for any diseases or disorders.
The application of this method is not limited to diseases where
antigenic shift or drift keeps the immune system guessing making it
slow to respond. Although, influenza or aids are likely candidates
other diseases, disorders and/or conditions will likely benefit
from this methodology. Other modifications of the subject matter
herein will be appreciated by one of skill in the art in light of
the teachings herein.
[0101] Those having skill in the art will recognize that the
present application teaches modifications of the devices,
structures, and/or processes within the spirit of the teaching
herein. For example, in one aspect, real-time evaluation may be
provided of the antigenic changes by including a portable PCR
machine which samples the environment for strains locally present.
The information may be sent remotely to another location or to a
portable drip patch utilized by the person resulting in the
activation of the necessary immune response components providing
adequate protection. As the evaluation changes the portable drip
patch may be triggered to change the dosage or type of immune
response component delivered. Such a portable drip patch
operably-coupled to a portable PCR machine has wide variety of
application, for example, including, but not limited to, when
medical personnel visit areas endemic to a disease, or when
military personnel visit hostile territory. Other modifications of
the subject matter herein will be appreciated by one of skill in
the art in light of the teachings herein.
[0102] Those having skill in the art will recognize that the
present application teaches modifications of the devices,
structures, and/or processes within the spirit of the teaching
herein. For example, in one aspect, an individual may use a
drip-patch infused with the immune response components
preprogrammed to provide the user the necessary protection over a
period of time, and to anticipate pattern changes in the epitopes
of the agent 100. Other modifications of the subject matter herein
will be appreciated by one of skill in the art in light of the
teachings herein.
[0103] Those having skill in the art will recognize that the
present application teaches modifications of the devices,
structures, and/or processes within the spirit of the teaching
herein. For example, in one aspect, RNA blockers, or single
stranded RNAI technology may be used to downregulate genes or
components of the immune system in conjunction with the method.
Other modifications of the subject matter herein will be
appreciated by one of skill in the art in light of the teachings
herein.
[0104] Those skilled in the art will appreciate that the foregoing
specific exemplary processes and/or devices and/or technologies are
representative of more general processes and/or devices and/or
technologies taught elsewhere herein, such as in the claims filed
herewith and/or elsewhere in the present application.
[0105] Those having skill in the art will recognize that the state
of the art has progressed to the point where there is little
distinction left between hardware and software implementations of
aspects of systems; the use of hardware or software is generally
(but not always, in that in certain contexts the choice between
hardware and software can become significant) a design choice
representing cost vs. efficiency tradeoffs. Those having skill in
the art will appreciate that there are various vehicles by which
processes and/or systems and/or other technologies described herein
can be effected (e.g., hardware, software, and/or firmware), and
that the preferred vehicle will vary with the context in which the
processes and/or systems and/or other technologies are deployed.
For example, if an implementer determines that speed and accuracy
are paramount, the implementer may opt for a mainly hardware and/or
firmware vehicle; alternatively, if flexibility is paramount, the
implementer may opt for a mainly software implementation; or, yet
again alternatively, the implementer may opt for some combination
of hardware, software, and/or firmware. Hence, there are several
possible vehicles by which the processes and/or devices and/or
other technologies described herein may be effected, none of which
is inherently superior to the other in that any vehicle to be
utilized is a choice dependent upon the context in which the
vehicle will be deployed and the specific concerns (e.g., speed,
flexibility, or predictability) of the implementer, any of which
may vary.
[0106] The foregoing detailed description has set forth various
embodiments of the devices and/or processes via the use of block
diagrams, flowcharts, and/or examples. Insofar as such block
diagrams, flowcharts, and/or examples contain one or more functions
and/or operations, it will be understood by those within the art
that each function and/or operation within such block diagrams,
flowcharts, or examples can be implemented, individually and/or
collectively, by a wide range of hardware, software, firmware, or
virtually any combination thereof. In one embodiment, several
portions of the subject matter described herein may be implemented
via Application Specific Integrated Circuits (ASICs), Field
Programmable Gate Arrays (FPGAs), digital signal processors (DSPs),
or other integrated formats. However, those skilled in the art will
recognize that some aspects of the embodiments disclosed herein, in
whole or in part, can be equivalently implemented in standard
integrated circuits, as one or more computer programs running on
one or more computers (e.g., as one or more programs running on one
or more computer systems), as one or more programs running on one
or more processors (e.g., as one or more programs running on one or
more microprocessors), as firmware, or as virtually any combination
thereof, and that designing the circuitry and/or writing the code
for the software and or firmware would be well within the skill of
one of skill in the art in light of this disclosure. In addition,
those skilled in the art will appreciate that the mechanisms of the
subject matter described herein are capable of being distributed as
a program product in a variety of forms, and that an illustrative
embodiment of the subject matter subject matter described herein
applies equally regardless of the particular type of signal bearing
media used to actually carry out the distribution. Examples of a
signal bearing media include, but are not limited to, the
following: recordable type media such as floppy disks, hard disk
drives, CD ROMs, digital tape, and computer memory; and
transmission type media such as digital and analog communication
links using TDM or IP based communication links (e.g., packet
links).
[0107] In a general sense, those skilled in the art will recognize
that the various aspects described herein which can be implemented,
individually and/or collectively, by a wide range of hardware,
software, firmware, or any combination thereof can be viewed as
being composed of various types of "electrical circuitry."
Consequently, as used herein "electrical circuitry" includes, but
is not limited to, electrical circuitry having at least one
discrete electrical circuit, electrical circuitry having at least
one integrated circuit, electrical circuitry having at least one
application specific integrated circuit, electrical circuitry
forming a general purpose computing device configured by a computer
program (e.g., a general purpose computer configured by a computer
program which at least partially carries out processes and/or
devices described herein, or a microprocessor configured by a
computer program which at least partially carries out processes
and/or devices described herein), electrical circuitry forming a
memory device (e.g., forms of random access memory), and/or
electrical circuitry forming a communications device (e.g., a
modem, communications switch, or optical-electrical equipment).
[0108] Those skilled in the art will recognize that it is common
within the art to describe devices and/or processes in the fashion
set forth herein, and thereafter use standard engineering practices
to integrate such described devices and/or processes into data
processing systems. That is, at least a portion of the devices
and/or processes described herein can be integrated into a data
processing system via a reasonable amount of experimentation. Those
having skill in the art will recognize that a typical data
processing system generally includes one or more of a system unit
housing, a video display device, a memory such as volatile and
non-volatile memory, processors such as microprocessors and digital
signal processors, computational entities such as operating
systems, drivers, graphical user interfaces, and applications
programs, one or more interaction devices, such as a touch pad or
screen, and/or control systems including feedback loops and control
motors (e.g., feedback for sensing position and/or velocity;
control motors for moving and/or adjusting components and/or
quantities). A typical data processing system may be implemented
utilizing any suitable commercially available components, such as
those typically found in data computing/communication and/or
network computing/communication systems.
[0109] All of the referenced U.S. patents, U.S. patent application
publications, U.S. patent applications, foreign patents, foreign
patent applications, and/or non-patent publications referred to in
this specification and/or listed in any Application Data Sheet, are
incorporated herein by reference, in their entireties.
[0110] The herein described aspects depict different components
contained within, or connected with, different other components. It
is to be understood that such depicted architectures are merely
exemplary, and that in fact many other architectures can be
implemented which achieve the same functionality. In a conceptual
sense, any arrangement of components to achieve the same
functionality is effectively "associated" such that the desired
functionality is achieved. Hence, any two components herein
combined to achieve a particular functionality can be seen as
"associated with" each other such that the desired functionality is
achieved, irrespective of architectures or intermedial components.
Likewise, any two components so associated can also be viewed as
being "operably connected", or "operably coupled", to each other to
achieve the desired functionality, and any two components capable
of being so associated can also be viewed as being "operably
couplable", to each other to achieve the desired functionality.
Specific examples of operably couplable include but are not limited
to physically mateable and/or physically interacting components
and/or wirelessly interactable and/or wirelessly interacting
components.
[0111] While particular aspects of the present subject matter
described herein have been shown and described, it will be apparent
to those skilled in the art that, based upon the teachings herein,
changes and modifications may be made without departing from this
subject matter described herein and its broader aspects and,
therefore, the appended claims are to encompass within their scope
all such changes and modifications as are within the true spirit
and scope of this subject matter described herein. Furthermore, it
is to be understood that the invention is solely defined by the
appended claims. It will be understood by those within the art
that, in general, terms used herein, and especially in the appended
claims (e.g., bodies of the appended claims) are generally intended
as "open" terms (e.g., the term "including" should be interpreted
as "including but not limited to," the term "having" should be
interpreted as "having at least," the term "includes" should be
interpreted as "includes but is not limited to," etc.). It will be
further understood by those within the art that if a specific
number of an introduced claim recitation is intended, such an
intent will be explicitly recited in the claim, and in the absence
of such recitation no such intent is present. For example, as an
aid to understanding, the following appended claims may contain
usage of the introductory phrases "at least one" and "one or more"
to introduce claim recitations. However, the use of such phrases
should not be construed to imply that the introduction of a claim
recitation by the indefinite articles "a" or "an" limits any
particular claim containing such introduced claim recitation to
inventions containing only one such recitation, even when the same
claim includes the introductory phrases "one or more" or "at least
one" and indefinite articles such as "a" or "an" (e.g., "a" and/or
"an" should typically be interpreted to mean "at least one" or "one
or more"); the same holds true for the use of definite articles
used to introduce claim recitations. In addition, even if a
specific number of an introduced claim recitation is explicitly
recited, those skilled in the art will recognize that such
recitation should typically be interpreted to mean at least the
recited number (e.g., the bare recitation of "two recitations,"
without other modifiers, typically means at least two recitations,
or two or more recitations). Furthermore, in those instances where
a convention analogous to "at least one of A, B, and C, etc." is
used, in general such a construction is intended in the sense one
having skill in the art would understand the convention (e.g., "a
system having at least one of A, B, and C" would include but not be
limited to systems that have A alone, B alone, C alone, A and B
together, A and C together, B and C together, and/or A, B, and C
together, etc.). In those instances where a convention analogous to
"at least one of A, B, or C, etc." is used, in general such a
construction is intended in the sense one having skill in the art
would understand the convention (e.g., "a system having at least
one of A, B, or C" would include but not be limited to systems that
have A alone, B alone, C alone, A and B together, A and C together,
B and C together, and/or A, B, and C together, etc.).
* * * * *
References